Prior studies have shown that certain regions of the adult central nervous system (CNS) process capabilities for reorganization of inter-neuronal circuitry in response to tissue damage. This structural reorganization of synaptic interarticulation may be in part responsible for limited functional recovery of lesion-induced deficits. Factors which may enhance or retard such recovery of CNS structure and function include the effects of hormones and form a basis for the present study of chronic glucocorticoid therapy and its role in lesion-induced changes in CNS circuitry. Adult rats will receive subcutaneous implants of osmotic mini-pumps containing various concentrations of corticosterone (CORT), dexamethasone and deoxycorticosterone following unilateral ablation of their entorhinal cortex. Changes in the hippocampal commissural-associational (C/A) system will be monitored by sensitive neuroanatomical and histochemical methods which previously have delineated changes in the time course of the reactive response involving axonal sprouting and synaptogenesis following unilateral hippocampal lesions. Detailed qualitative and quantitative analysis of this region will be performed using light and electron microscopy in association with sensitive laminar microchemical techniques in order to determine the effects of adrenalcorticoid treatment on the rate of synapse replacement. By assessing the critical period for therapeutic intervention with various adrenal steroids, information on the optimal mode of treatment designed to promote appropriate synapse formation will be gathered. Moreover, by providing a more detailed quantitative analysis of restoration of fine structure of the neuropil at various intervals after CNS damage, it will be possible to gain information on the rate and magnitude of synapse formation as affected by glucocorticoids. Preliminary light and electron microscopic observations indicate that CORT has a pronounced effect on axon sprouting in the dentate gyrus. Structural reconstitution of this area after lesion-induced synaptogenesis will be reliably assessed by microchemical changes in association with light and electron microscopy and will certainly contribute to our understanding of the role of glucocorticoids on axon sprouting. Since steroid hormones are clinically used to control "brain edema" this study has obvious and important clinical implications.